When to initiate Non-Vitamin K Antagonist Oral Anticoagulant (NOAC) therapy after an ischemic stroke?

From the Guidelines

The timing to start a Non-Vitamin K Antagonist Oral Anticoagulant (NOAC) after a stroke should be based on the stroke severity, with initiation recommended at 1 day after a transient ischaemic attack (TIA), >3 days after a mild stroke, >6-8 days after a moderate stroke, and >12-14 days after a severe stroke, as stated in the 2018 European Heart Rhythm Association practical guide 1. When deciding on the timing of NOAC initiation after a stroke, several factors should be considered, including the risk of recurrent stroke and the risk of secondary haemorrhagic transformation.

• The risk of recurrent stroke should be weighed against the risk of secondary haemorrhagic transformation, with the goal of minimizing both risks.
• Brain imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI), should be used to exclude secondary haemorrhagic transformation before initiating NOAC therapy.
• The dose of the NOAC should be appropriate for the patient's renal function, with dose adjustments made as necessary to minimize the risk of bleeding.
• The use of 'bridging' with heparin (LMWH or UFH) is not recommended due to the rapid onset of action of NOACs and the associated risk of bleeding, as noted in the 2018 European Heart Rhythm Association practical guide 1.
• Common NOACs include apixaban, rivaroxaban, dabigatran, and edoxaban, with dosing regimens varying depending on the specific medication and patient factors. The decision to start a NOAC after a stroke should be individualized, taking into account the patient's specific clinical characteristics and the potential risks and benefits of therapy, as recommended in the 2018 European Heart Rhythm Association practical guide 1.

From the Research

Timing of NOAC Initiation After Acute Ischemic Stroke

• The optimal time to start Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) after an acute ischemic stroke in patients with atrial fibrillation is uncertain 2, 3.
• Current guidelines do not provide evidence-based recommendations on the optimal time-point to start anticoagulation therapy after an acute ischemic stroke 2.
• Studies suggest that early initiation of anticoagulation after a transient ischemic attack (TIA), small-, or medium-sized acute ischemic stroke from atrial fibrillation does not appear to compromise patient safety 4.
• The risk of hemorrhagic transformation of an acute ischemic stroke may be increased with early initiation of anticoagulation, particularly within 48 hours of stroke onset 3.
• Infarct size and presence of hemorrhage are important factors in identifying the optimal time to initiate anticoagulation and should guide decisions when available 3.

Factors Influencing NOAC Initiation

• Large ischemic lesions, cerebral microbleeds, thrombolytic therapy, and other clinical factors may increase the risk of hemorrhagic transformation of an acute ischemic stroke 3.
• Parenteral anticoagulation within 48 hours is associated with an increased risk of hemorrhagic transformation and is not recommended 3.
• The use of apixaban, a type of NOAC, has been shown to have a similar or better safety profile compared to warfarin in patients with nonvalvular atrial fibrillation and previous stroke or transient ischemic attack 5, 6.

Clinical Trials and Studies

• The TIMING study, a randomized controlled trial, aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and atrial fibrillation 2.
• The AREST trial, an open-label, randomized controlled trial, compared the safety of early use of apixaban with warfarin in patients with atrial fibrillation and stroke or transient ischemic attack 4.
• Real-world studies have shown that apixaban is effective in reducing thromboembolic events and stroke, with a lower risk of major bleeding compared to warfarin, dabigatran, and rivaroxaban 6.